Propantheline

Class: Antimuscarinics/Antispasmodics
VA Class: AU350
CAS Number: 50-34-0

Medically reviewed by Drugs.com on May 24, 2021. Written by ASHP.

Introduction

Synthetic quaternary ammonium antimuscarinic.

Uses for Propantheline

Peptic Ulcer Disease

Adjunctive therapy in the treatment of peptic ulcer disease; however, no conclusive data that propantheline aids in the healing, decreases the rate of recurrence, or prevents complications of peptic ulcers.

With the advent of more effective therapies for the treatment of peptic ulcer disease, antimuscarinics have only limited usefulness in this condition.

Propantheline Dosage and Administration

Administration

Administer orally, preferably 30 minutes before meals and at bedtime.

Has also been administered IV or IM; however, a parenteral preparation is no longer commercially available in the US.

Dosage

Available as propantheline bromide; dosage expressed in terms of the salt.

As with other antimuscarinics, higher than recommended dosage may be required for therapeutic effect. Titrate dosage until therapeutic effect is achieved or adverse effects become intolerable (using the lowest possible effective dosage).

Adults

Peptic Ulcer Disease

Oral

15 mg taken 30 minutes prior to each meal (3 times daily) and 30 mg at bedtime (total of 75 mg daily).

In cases of mild manifestations or for patients of small stature: 7.5 mg 30 minutes before each meal (3 times daily) has been used, but this strength tablet is not currently commercially available. One manufacturer (Roxane) states that it may be possible to break the 15-mg film-coated tablets in half without substantially damaging the tablets.

Adjust dosage according to patient response and tolerance.

Special Populations

Hepatic Impairment

No special population dosage recommendations at this time.

Renal Impairment

No special population dosage recommendations at this time.

Geriatric Patients

7.5 mg taken 30 minutes prior to each meal (3 times daily) has been used, but this strength tablet is not currently commercially available. One manufacturer (Roxane) states that it may be possible to break the 15-mg film-coated tablets in half without substantially damaging the tablets.

Cautions for Propantheline

Contraindications

Glaucoma (to avoid mydriasis).
Obstructive GI disease (e.g., pyloroduodenal stenosis, achalasia, paralytic ileus).
Obstructive uropathy (e.g., bladder neck obstruction caused by prostatic hypertrophy).
Intestinal atony (especially in geriatric or debilitated patients).
Severe ulcerative colitis or toxic megacolon complicating ulcerative colitis.
Acute hemorrhage when cardiovascular status is unstable.
Myasthenia gravis.

Warnings/Precautions

Warnings

Thermoregulatory Effects

Exposure to high environmental temperatures may result in heat prostration (e.g., fever, heat stroke) due to decreased sweating. Increased risk of hyperthermia in febrile patients. (See Advice to Patients.)

Diarrhea

May be an early sign of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. Do not use in such patients; use would be inappropriate and possibly harmful.

Overdosage

A curare-like action may occur (i.e., neuromuscular blockade leading to muscular weakness and possible paralysis).

Large or toxic doses may produce marked CNS disturbances (e.g., restlessness, excitement, psychotic behavior), circulatory changes (e.g., flushing, hypotension, circulatory failure), respiratory failure, paralysis, and coma.

Cardiovascular Effects

May increase heart rate. Use with caution in patients with heart disease.

Sensitivity Reactions

Hypersensitivity Reactions

Risk of severe allergic or idiosyncratic reactions (e.g., anaphylaxis, urticaria, other dermatologic manifestations).

General Precautions

CNS Effects

Risk of drowsiness or blurred vision. Performance of activities requiring mental alertness and physical coordination (e.g., operating a vehicle or other machinery, performing hazardous work) may be impaired. (See Advice to Patients.)

GI Effects

Caution in patients with gastric ulcer because of delayed gastric emptying and possible antral stasis.

Caution in patients with hiatal hernia associated with reflux esophagitis; anticholinergics may aggravate this condition.

Caution in patients with ulcerative colitis. Large doses may suppress intestinal motility resulting in paralytic ileus and causing or precipitating toxic megacolon.

Concomitant Illnesses

Use with caution in patients with hyperthyroidism, autonomic neuropathy, CHD, CHF, cardiac tachyarrhythmia, or hypertension.

Specific Populations

Pregnancy

Category C.

Lactation

Not known if propantheline is distributed into human milk. Caution if used in nursing women.

May suppress lactation.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

Use with caution.

Hepatic Impairment

Use with caution in patients with hepatic disease.

Renal Impairment

Use with caution in patients with renal disease.

Common Adverse Effects

Xerostomia, decreased sweating, adverse ophthalmic effects (e.g., blurred vision, mydriasis, cycloplegia, increased ocular tension).

Interactions for Propantheline

Drugs with Anticholinergic Effects

Additive adverse effects resulting from cholinergic blockade (e.g., xerostomia, blurred vision, constipation). Advise of possibility of increased anticholinergic effects.

Orally Administered Drugs

Potential pharmacokinetic interaction (altered GI absorption of various drugs). Antimuscarinics may inhibit GI motility, delay gastric emptying, and prolong GI transit time.

Specific Drugs

Drug	Interaction	Comments
Acetaminophen	Decrease rate but not extent of acetaminophen absorption; may delay onset of acetaminophen therapeutic effects
Antacids	Possible decreased absorption of antimuscarinic	Administer at least 1 hour before antacids
Antiarrhythmic agents, type I (e.g., disopyramide, procainamide, quinidine)	Possible additive adverse anticholinergic effects	Inform patient of possibility
Antidepressants, tricyclic	Possible additive adverse anticholinergic effects	Inform patient of possibility
Antihistamines	Possible additive adverse anticholinergic effects	Inform patient of possibility
Antiparkinsonian agents	Possible additive adverse anticholinergic effects	Inform patient of possibility
Belladonna alkaloids	Possible additive adverse anticholinergic effects
Corticosteroids	Possible increased IOP
Digoxin	Increased serum digoxin concentration with slowly dissolving digoxin tablets	Use digoxin oral solution or rapidly dissolving tablets; observe for signs of digoxin toxicity
Ketoconazole	Possible decreased ketoconazole absorption	Administer antimuscarinic ≥2 hours after ketoconazole
Levodopa	Possible increased gastric levodopa metabolism, resulting in decreased levodopa absorption	Possible levodopa toxicity if antimuscarinic is discontinued without a concomitant reduction in levodopa dosage
Meperidine	Possible additive adverse anticholinergic effects	Inform patient of possibility
Phenothiazines	Possible additive adverse anticholinergic effects; possible potentiation of sedative effects	Inform patient of possibility
Potassium chloride	Antimuscarinics may slow GI transit, increasing risk of potassium chloride GI mucosal toxicity	Administer concomitantly with caution (especially with wax matrix potassium chloride preparations)
Riboflavin	Delayed rate but increased extent of riboflavin absorption reported

Propantheline Pharmacokinetics

Absorption

Bioavailability

Incompletely absorbed from the GI tract because completely ionized.

Peak plasma concentrations occur about one hour after a single oral dose.

Food

Extent of absorption is substantially decreased by food.

Distribution

Possesses poor lipid solubility. Limited ability to distribute into CNS or eye.

Not known whether propantheline is distributed into milk.

Elimination

Metabolism

Extensively metabolized, primarily by hydrolysis, to the inactive compounds xanthene-9-carboxylic acid and (2-hydroxyethyl) diisopropylmethylammonium bromide.

Elimination Route

70% of the dose is excreted in the urine, mostly as metabolites.

Half-life

Elimination half-life: 1.6 hours.

Stability

Storage

Oral

Tablets

20–25°C.

Actions

Competitively inhibits acetylcholine or other cholinergic stimuli at autonomic effectors innervated by postganglionic cholinergic nerves and, to a lesser extent, on smooth muscles that lack cholinergic innervation.
At usual doses, antimuscarinics principally antagonize cholinergic stimuli at muscarinic receptors and have little or no effect on cholinergic stimuli at nicotinic receptors.
Antimuscarinics also have been referred to as anticholinergics (cholinergic blocking agents), but this term is appropriate only when it describes the antagonism of cholinergic stimuli at any cholinergic receptor, whether muscarinic or nicotinic.
Antimuscarinics also have been referred to as parasympatholytics since the antagonized functions principally are under the parasympathetic division of the nervous system.
Inhibits GI motility and diminishes gastric acid secretion.
Inhibits the action of acetylcholine at the postganglionic nerve endings of the parasympathetic nervous system.

Advice to Patients

Potential for hyperthermia and heat prostration; avoid exposure to high environmental temperature and use with caution when febrile.
Risk of drowsiness or blurred vision; exercise caution when performing activities requiring mental alertness (e.g., driving a motor vehicle, operating machinery) or when performing other hazardous work.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name